Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis E virus (HEV) is a polyadenylated, positive-stranded RNA virus which is a major cause of enterically transmitted non-A, non-B hepatitis in many developing countries. The viral genome contains three different open reading frames (ORFs): ORF1, which is believed to encode nonstructural proteins, and ORF2 and ORF3, which are believed to encode structural proteins. The full-length putative structural proteins encoded by ORF2 and ORF3 of HEV have been cloned and expressed in recombinant vaccinia virus. Proteins encoded by ORF2 and ORF3 when expressed in vaccinia virus are recognized by pooled sera obtained from individuals with acute hepatitis E. Vaccinia-expressed viral gene products of HEV will have utility in characterizing the cell-mediated immune response to HEV.
 ...
PMID:Expression of hepatitis E virus putative structural proteins in recombinant vaccinia viruses. 749 58

Thirteen monoclonal antibodies (Mab) specific for the nucleocapsid (N) protein of mouse hepatitis virus were mapped using a panel of carboxy-terminal N protein truncations expressed by recombinant vaccinia viruses. All of the Mab recognized both native protein and full-length N protein expressed in this vector by both Western blot and enzyme-linked immunoabsorbent assays (ELISA), indicating that they recognized linear epitopes. The results obtained by both Western blot and ELISA for binding to the truncated N proteins coincide for seven of the Mab tested. The linear epitopes recognized localize to four domains dispersed between amino acids 171 and 196, 231 and 277, and 374 and 455. The epitopes for six Mab were localized to domains comprising 29 amino acids or less as determined by ELISA. Seven Mab showed different reactivity patterns in Western blot versus ELISA, suggesting binding may be influenced by local conformation. Therefore, the fine specificity of these Mab could not be determined with certainty. These data represent the first determination of antibody binding domains within the mouse hepatitis virus N protein which forms the viral helical nucleocapsids and appears to perform a number of regulatory functions during virus replication.
 ...
PMID:Location of antibody epitopes within the mouse hepatitis virus nucleocapsid protein. 751 95

Chimeric peptides in which the optimal H-2d mouse hepatitis virus nucleocapsid (pN) and human immunodeficiency virus type 1 (p18) epitopes, separated by 38, 7, or 2 amino acids, were expressed from a single open reading frame by using recombinant vaccinia viruses to analyze antigen processing of proximal class I-restricted epitopes. Recognition of the carboxy-terminal Dd-restricted p18 epitope was independent of the amino-terminal flanking residues. By contrast, proximity of the carboxy-terminal epitope decreased recognition of the amino-terminal Ld-restricted pN epitope. Immunization resulted in the induction of both p18- and pN-specific antiviral cytotoxic T lymphocytes, irrespective of the number of amino acids separating the epitopes.
 ...
PMID:Differential effects of flanking residues on presentation of epitopes from chimeric peptides. 751 34

The intrahepatic accumulation of the c-myc protooncogene product was observed on immunofluorescence in each of six patients with chronic hepatitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that contained the hepatitis D antigen. C-myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was detected in only 1 of 32 viral and nonviral liver disorders unrelated to hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with a plasmid containing a hepatitis delta virus cDNA trimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-transfected PLC/PRF/5 or HepG2 cells, strong c-myc nuclear fluorescence was observed when these same cells were transfected with the hepatitis D antigen expression vector. Similar results were obtained after infection of HeLa cells with a recombinant vaccinia virus expressing the hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not due to increased amounts of its mRNA. The c-myc protein accumulates selectively in the livers of patients with chronic hepatitis delta virus infection and in the same nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis D antigen-containing cells does not require the presence of hepatitis B virus infection.
 ...
PMID:Expression of the c-myc protooncogene product in cells infected with the hepatitis delta virus. 752 69

Coronaviruses are assembled by budding into smooth membranes of the intermediate ER-to-Golgi compartment. We have studied the association of the viral membrane glycoproteins M and S in the formation of the virion envelope. Using coimmunoprecipitation analysis we demonstrated that the M and S proteins of mouse hepatitis virus (MHV) interact specifically forming heteromultimeric complexes in infected cells. These could be detected only when the detergents used for their solubilization from cells or virions were carefully chosen: a combination of nonionic (NP-40) and ionic (deoxycholic acid) detergents proved to be optimal. Pulse-chase experiments revealed that newly made M and S proteins engaged in complex formation with different kinetics. Whereas the M protein appeared in complexes immediately after its synthesis, newly synthesized S protein did so only after a lag phase of > 20 min. Newly made M was incorporated into virus particles faster than S, which suggests that it associates with preexisting S molecules. Using the vaccinia virus T7-driven coexpression of M and S we also demonstrate formation of M/S complexes in the absence of other coronaviral proteins. Pulse-chase labelings and coimmunoprecipitation analyses revealed that M and S associate in pre-Golgi membranes because the unglycosylated form of M appeared in M/S complexes rapidly. Since no association of M and S was detected when protein export from the ER was blocked by brefeldin A, stable complexes most likely arise in the ER-to-Golgi intermediate compartment. Sucrose velocity gradient analysis showed the M/S complexes to be heterogeneous and of higher order, suggesting that they are maintained by homo- and heterotypic interactions. M/S complexes colocalized with alpha-mannosidase II, a resident Golgi protein. They acquired Golgi-specific oligosaccharide modifications but were not detected at the cell surface. Thus, the S protein, which on itself was transported to the plasma membrane, was retained in the Golgi complex by its association with the M protein. Because coronaviruses bud at pre-Golgi membranes, this result implies that the envelope glycoprotein complexes do not determine the site of budding. Yet, the self-association of the MHV envelope glycoproteins into higher order complexes is indicative of its role in the sorting of the viral membrane proteins and in driving the formation of the viral lipoprotein coat in virus assembly.
 ...
PMID:Envelope glycoprotein interactions in coronavirus assembly. 759 63

Hepatitis C virus (HCV) is the major cause of transfusion-acquired non-A, non-B hepatitis. HCV is an enveloped positive-sense RNA virus which has been classified as a new genus in the flavivirus family. Like the other two genera in this family, the flaviviruses and the pestiviruses, HCV polypeptides appear to be produced by translation of a long open reading frame and subsequent proteolytic processing of this polyprotein. In this study, a cDNA clone encompassing the long open reading frame of the HCV H strain (3,011 amino acid residues) has been assembled and sequenced. This clone and various truncated derivatives were used in vaccinia virus transient-expression assays to map HCV-encoded polypeptides and to study HCV polyprotein processing. HCV polyproteins and cleavage products were identified by using convalescent human sera and a panel of region-specific polyclonal rabbit antisera. Similar results were obtained for several mammalian cell lines examined, including the human HepG2 hepatoma line. The data indicate that at least nine polypeptides are produced by cleavage of the HCV H strain polyprotein. Putative structural proteins, located in the N-terminal one-fourth of the polyprotein, include the capsid protein C (21 kDa) followed by two possible virion envelope proteins, E1 (31 kDa) and E2 (70 kDa), which are heavily modified by N-linked glycosylation. The remainder of the polyprotein probably encodes nonstructural proteins including NS2 (23 kDa), NS3 (70 kDa), NS4A (8 kDa), NS4B (27 kDa), NS5A (58 kDa), and NS5B (68 kDa). An 82- to 88-kDa glycoprotein which reacted with both E2 and NS2-specific HCV antisera was also identified (called E2-NS2). Preliminary results suggest that a fraction of E1 is associated with E2 and E2-NS2 via disulfide linkages.
 ...
PMID:Expression and identification of hepatitis C virus polyprotein cleavage products. 767 46

The mouse hepatitis virus (MHV) JHM strain (JHMV) produces primary demyelination in the central nervous system associated with acute encephalomyelitis. Humoral and cellular immune responses both participate in controlling the development of chronic MHV-induced demyelination. A subset of the CD8+ cytotoxic T lymphocytes (CTL) induced by immunization of BALB/c (H-2d) mice with JHMV is specific for the viral nucleocapsid protein. This CTL population recognizes an epitope located within the carboxy-terminal 149 amino acids in association with the Ld class I molecule (S. A. Stohlman, S. Kyuwa, M. Cohen, C. Bergmann, J. P. Polo, J. Yeh, R. Anthony, and J. G. Keck, Virology 189:217-224, 1992). Using a panel of vaccinia virus recombinants expressing truncated forms of the nucleocapsid protein and a series of overlapping synthetic peptides, we mapped the response to 15 amino acids. This sequence, encompassing the MHV epitope, contains the Ld-specific binding motif. The predicted 9-mer peptide (residues 318 to 326: APTAGAFFF) was sufficient and highly active in sensitizing target cells for CTL recognition when either added exogenously or synthesized intracellularly. Cross-reactivity of JHMV nucleocapsid protein-specific CTL with six other MHV strains indicated that natural sequence variations within the 9-mer epitope are tolerated in positions 4 and 5, whereas all other amino acids are conserved. These data define a novel 9-mer Ld-restricted CTL epitope which represents the first MHV CTL epitope. Characterization of this epitope provides a molecular basis to study the role of nucleocapsid protein-specific CTL in the clearance of JHMV from the central nervous system.
 ...
PMID:Characterization of the Ld-restricted cytotoxic T-lymphocyte epitope in the mouse hepatitis virus nucleocapsid protein. 769 65

Hepatitis C virus (HCV) is a major cause of posttransfusion and community-acquired hepatitis, and a majority of individuals infected with this virus will subsequently develop chronic hepatitis. Characterization of the host immune response to this infection is an important first step that should facilitate the development of immunomodulatory agents and vaccines. Cellular immune responses, especially those mediated by cytotoxic T lymphocytes (CTL), are important in the control of many viral diseases. In this study, liver-infiltrating lymphocytes from persons with chronic HCV hepatitis were examined for evidence of HCV-specific CTL by using target cells infected with recombinant vaccinia viruses expressing the HCV core, E1, E2, and part of the NS2 proteins. Bulk expansion of liver-derived CD8+ lymphocytes resulted in the detection of HCV-specific CTL activity, whereas activity could not be found in CD8+ lymphocytes expanded from peripheral blood. Epitopes recognized by these CTL were defined by using CTL clones obtained by limiting dilution and target cells sensitized with synthetic HCV peptides. Four distinct HLA class I-restricted epitopes were identified, including two epitopes in the amino-terminal portion of the core protein. These studies provide evidence that the highly conserved core protein is a target for HCV-specific CTL and identify CTL epitopes within the more highly variable E2 envelope protein. Our studies also suggest that HCV-specific CTL are localized at the site of tissue injury in infected persons with chronic hepatitis. Identification of the epitopes recognized by HCV-specific CTL will facilitate exploration of their role in disease pathogenesis and may provide information useful in development of therapeutic interventions or vaccines.
 ...
PMID:Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. 769 74

We have previously demonstrated molecular mimicry between the S peplomer protein of mouse hepatitis virus (MHV) and Fc gamma R (Fc gamma R). A monoclonal antibody (MAb) to mouse Fc gamma R (2.4G2 anti-Fc gamma R MAb), purified rabbit immunoglobulin, but not their F(ab')2 fragments, as well as mouse and rat IgG, immunoprecipitated (1) recombinant S peplomer protein expressed by a vaccinia virus recombinant in human, rabbit, and mouse cells, and (2) natural S peplomer protein from cells infected with several strains of MHV and MHV escaped mutants. We report here results of studies documenting molecular mimicry between Fc gamma R and S peplomer protein of viruses representing three distinct antigenic subgroups of the Coronaviridae. We have shown a molecular mimicry between the S peplomer protein of bovine corona virus (BCV) and Fc gamma R. The 2.4G2 anti-Fc gamma R MAb, rabbit IgG, but not its F(ab')2 fragments, as well as homologous bovine serum, free of anti-BCV antibodies, immunoprecipitated S peplomer protein of BCV (Mebus strain). In contrast, we did not find molecular mimicry between S peplomer protein of human corona virus (HCV-OC43) and Fc gamma R. Although the OC43 virus belongs to the same antigenic group as MHV and BCV, MAb specific for human Fc gamma RI or Fc gamma RII and purified human IgG1, IgG2, and IgG3 myeloma proteins did not immunoprecipitate the S peplomer protein from HCV-OC43-infected RD cells. In addition, we did demonstrate molecular mimicry between the S peplomer protein of porcine transmissible gastroenteritis virus (TGEV) and Fc gamma R. TGEV belongs to the second antigenic subgroup of coronaviridae.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Molecular mimicry between Fc receptor and S peplomer protein of mouse hepatitis virus, bovine corona virus, and transmissible gastroenteritis virus. 776 29

The carboxyl-terminal Lys-Asp-Glu-Leu (KDEL), or a closely-related sequence, is important for ER localization of both lumenal as well as type II membrane proteins. This sequence functions as a retrieval signal at post-ER compartment(s), but the exact compartment(s) where the retrieval occurs remains unresolved. With an affinity-purified antibody against the carboxyl-terminal sequence of the mammalian KDEL receptor, we have investigated its subcellular localization using immunogold labeling on thawed cryosections of different tissues, such as mouse spermatids and rat pancreas, as well as HeLa, Vero, NRK, and mouse L cells. We show that rab1 is an excellent marker of the intermediate compartment, and we use this marker, as well as budding profiles of the mouse hepatitis virus (MHV) in cells infected with this virus, to identify this compartment. Our results demonstrate that the KDEL receptor is concentrated in the intermediate compartment, as well as in the Golgi stack. Lower but significant labeling was detected in the rough ER. In general, only small amounts of the receptor were detected on the trans side of the Golgi stack, including the trans-Golgi network (TGN) of normal cells and tissues. However, some stress conditions, such as infection with vaccinia virus or vesicular stomatitis virus, as well as 20 degrees C or 43 degrees C treatment, resulted in a significant shift of the distribution towards the trans-TGN side of the Golgi stack. This shift could be quantified in HeLa cells stably expressing a TGN marker. No significant labeling was detected in structures distal to the TGN under all conditions tested. After GTP gamma S treatment of permeabilized cells, the receptor was detected in the beta-COP-containing buds/vesicles that accumulate after this treatment, suggesting that these vesicles may transport the receptor between compartments. We propose that retrieval of KDEL-containing proteins occurs at multiple post-ER compartments up to the TGN along the exocytotic pathway, and that within this pathway, the amounts of the receptor in different compartments varies according to physiological conditions.
 ...
PMID:Localization of the Lys, Asp, Glu, Leu tetrapeptide receptor to the Golgi complex and the intermediate compartment in mammalian cells. 779 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>